Recently, the uses of poly(l-lactide), poly(d-lactide), poly(dl-lactide), poly(ε-caprolactone), polyglycolide, and other high molecular weight copolymers in the production of biodegradable containers have increased dramatically due to concerns regarding non-degradable petrochemical products which cause severe environmental problems.
Generally, the synthesis of high molecular weight polyester requires ring-opening polymerization (ROP) of a cyclic ester monomer using tin(II) octoate (Sn(Oct)2) and an alcohol as the initiating system. There are two proposed mechanisms in this well-known process as suggested by 1) Kricheldorf and co-workers [Hans R. Kricheldorf, I. Kreiser-Saunders, and Caroline Boettcher, Polymer 1995, 36, 1253-1259, and Hans R. Kricheldorf, Ingrid Kreiser-Saunders, and Andrea Stricker, Macromolecules 2000, 33, 702-709] and 2) Penczek and co-workers [Adam Kowalski, Andrzej Duda, and Stanislaw Penczek, Macromol. Rapid Commun. 1998, 19, 567-572; Adam Kowalski, Andrzej Duda, and Stanislaw Penczek, Macromolecules 2000, 33, 689-695, and Adam Kowalski, Andrzej Duda, and Stanislaw Penczek, Macromolecules 2000, 33, 7359-7370]. Kricheldorf proposed the coordination of Sn(Oct)2 and the alcohol with the initial cyclic ester following by ring-opening polymerization. The former serves as a reagent whereas the latter is an initiator, as depicted in the following chemical equation:

In contrast, Penczek suggested the reaction between Sn(Oct)2 and the alcohol, resulting in the formation of Sn(Oct)(OR) and Sn(OR)2, the true initiators of this reaction as shown in the following chemical equations:
The latter mechanism has been widely accepted as the most reasonable mechanistic pathway. To produce high molecular weight polyesters via ring-opening polymerization, it is extremely important to know the exact concentration of the tin(II) alkoxide initiator which should be highly soluble in the cyclic ester monomer. For these reasons, our research group has been focusing on liquid tin(II) alkoxide derivatives which are soluble in common organic solvents and cyclic ester monomers.
Tin(II) alkoxides were firstly prepared by Amberger and Kula [Eberhard Amberger, Maria-Regina Kula, Chem. Ber. 1963, 96, 2562-2565] in 1963, using anhydrous tin(II) chloride to react with sodium methoxide (NaOCH3) in methanol as shown in the following equation:
White, hygroscopic solid tin(II) methoxide (Sn(OCH3)2) was obtained from this preparation. Later in 1967, Morrison and Haendler [James S. Morrison and Helmut M. Haendler, J. Inorg. Nucl. Chem. 1967, 29, 393-400] developed a more convenient synthetic method using tin(II) chloride dihydrate (SnCl2.2H2O, 6.0 g, 0.032 mol), dried with acetic anhydride ((CH3CO)2O). Dry tin(II) chloride was dissolved in anhydrous methanol (anh. CH3OH, 200 mL), under a nitrogen atmosphere. A solution of triethylamine (Et3N) was added slowly until the precipitation was complete. The resulting solution was filtered, washed several times with methanol to remove triethylamine hydrochloride and then washed with diethyl ether. The product was subsequently dried under reduced pressure. The overall chemical equation for this preparation may be represented as:
Tin(II) ethoxide (Sn(OCH2CH3)2) can be synthesized in a similar fashion. Tin(II) chloride dihydrate (3.0 g, 0.015 mol) was dissolved in anhydrous ethanol (CH3CH2OH, 75 mL). The white solid obtained turned yellow rapidly, even when the product was dried and kept under vacuum. Solubility tests showed that both tin(II) methoxide and tin(II) ethoxide dissolved only slightly in several organic solvents.
In 1975, Gsell and Zeldin [Ray Gsell and Martel Zeldin, J. Inorg. Nucl. Chem. 1975, 37, 1133-1137] prepared tin(II) n-butoxide (Sn(OnC4H9)2) via transesterification of tin(II) methoxide. Tin(II) methoxide was refluxed with excess n-butanol (n-C4H9OH) in toluene (C6H5CH3) until the solution became clear and colorless. Toluene and n-butanol were removed until the volume of solution was about 100 mL. The solution was cooled to room temperature and crystalline tin(II) n-butoxide was obtained, as shown in the following equation:
The tin(II) n-butoxide product was a white solid with a melting point of 171-172° C. and was extremely moisture and oxygen sensitive. As the alkyl chain became longer, such as in changing from CH3 to C2H5, the solubility of the product in organic solvents increased slightly. The physical and chemical properties relating to tin(II) methoxide, tin(II) ethoxide and tin(II) n-butoxide are summarized in Table 1, while their 1H-NMR spectroscopic data are shown in Table 2.
TABLE 1Molecular formulae, physical appearances, melting points and solubilities ofsolid tin(II) alkoxides synthesized by Gsell and Zeldin.Tin(II) alkoxideMolecular formulaPhysical appearancem.p. (° C.)/SolubilityTin(II) methoxideSn(OCH3)2White solid242-243° C./slightlydissolves in organicsolvents at roomtemperature but hardlydissolves in polarsolvents at hightemperatureTin(II) ethoxideSn(OC2H5)2White solidDecomposes at T >200° C.before the meltingpoint/insoluble in mostorganic solvents at roomtemperature but dissolvesin polar solvents such aso-dichlorobenzene athigh temperatureTin(II) n-butoxideSn(O—n-C4H9)2White solid171-172° C./partiallysoluble in organicsolvents
TABLE 21H-NMR data (220 MHz) of solid tin(II)alkoxides synthesized by Gsell and Zeldin.TempTin(II) alkoxideSolvent(° C.)Chemical shift (δ, ppm)Tin(II) methoxideo-C6H4Cl2756.5 (s, br)o-C6H4Cl21506.48 (s)Tin(II) ethoxide*o-C6H4Cl2351.17 (t), 1.23 (t), 3.80 (q), 3.99 (q)o-C6H4Cl21501.20 (t), 3.85 (q)†Tin(II)C6H6350.85 (t)‡, 1.30 (h, γ), 1.65 (q, β),n-butoxide*,‡,#3.80 (t, α)o-C6H4Cl21000.96 (t, δ)‡, 1.45 (h, γ), 1.72 (q, β),4.09 (t, α)(spectrum shown in the followingfigure)Note:*J = 7 Hz†The ratio of t/q = 1.5‡Recorded on NMR 220 MHz#Proton positions of CH3—CH2—CH2—CH2— are α, γ, β, and δ, respectively
In accordance with the U.S. Pat. No. 6,414,174 B1 (Jul. 2, 2002), Boyle and co-workers reported the preparation of a tin complex from the hydrolysis of tin(II) tert-butylmethoxide in the presence of a basic reagent. (Sn(N(CH3)2)2)2 was dissolved in hexane and two mole equivalence of tert-butylmethanol ((CH3)3CCH2OH) were added. The reaction mixture was stirred for 24 hours and then warmed for an additional 1 hour. All solvents were removed in vacuo and the product washed with hexane and recrystallized from hot tetrahydrofuran (THF). Tin(II) tert-butylmethoxide was obtained as a white solid in its polymeric form of ((Sn(OCH2C(CH3)3)2)n, which barely dissolved in tetrahydrofuran. Later, Boyle and co-workers carried out the hydrolysis of (Sn(OCH2C(CH3)3)2)n using water in the amounts of 0.50-0.75 and 0.30-0.50 mole equivalence relative to the starting material. The results showed that tin(II) tert-butylmethoxide was obtained in the forms of Sn6(O)4(OCH2C(CH3)3)4 and Sn5(O)2(OCH2C(CH3)3)6, respectively.
The major drawback of these tin(II) compounds, such as tin(II) alkoxide (Sn(OR)2) where R═CH3, C2H5, and n-C4H9, as reported by Morrison and Haendler, and Gsell and co-workers, is their poor solubility in common organic solvents in the temperature range of 25-35° C. Solubility increases in highly polar solvents and at higher temperatures. Moreover, tin(II) alkoxides synthesized by Morrison and Haendler's procedure using several alcohols such as CH3OH, C2H5OH, n-C3H7OH, n-C4H9OH, n-C6H13OH, and n-C8H17OH, are all white solids. Solubility test results for these tin(II) alkoxides in general organic solvents are summarized in Table 3. All of the tin(II) alkoxides are insoluble in all ten non-polar aprotic solvents but are slightly soluble in polar solvents when heated.
TABLE 3Solubility test results of tin(II) alkoxides in normal organic solvents.Methanol/Chloroform/acetone/toluene/tetrahy-Dimethyl sulfoxide/Tin(II) alkoxiden-heptanedrofurano-dichlorobenzeneSn(OCH3)2 (solid)xxxSn(OC2H5)2 (solid)xxxSn(O—n-C3H7)2 (solid)xx∘Sn(O—n-C4H9)2 (solid)xx∘Sn(O—n-C6H13)2 (solid)xx∘Sn(O—n-C8H17)2 (solid)xx∘Note:Solid tin(II) alkoxides were synthesized by the method reported by Morrison and Haendler.x is insoluble even when heat was applied∘ is slightly soluble upon heating✓ is completely soluble in the temperature range of 25-35° C.
The inventors have tried to synthesize tin(II) alkoxides with R groups of n-C4H9, n-C6H13 and n-C8H17 using the procedure reported by Gsell and Zeldin but no liquid tin(II) alkoxides could be obtained due to the tendency for self-aggregation of the tin(II) alkoxide molecules, as illustrated in the following figure:
The self-aggregation of tin(II) alkoxide molecules makes them insoluble and also inhibits their transesterification with the desired alcohols. Additionally, solid tin(II) alkoxides synthesized by the procedure reported by Morrison and Haendler contain significant amounts of triethylamine hydrochloride. This requires large quantities of alcohol to remove the salt by-product in the washing step, producing unnecessary and unwanted alcohol waste. Only moderate percent yields (˜50%) were obtained after the washing step. Due to their low solubility in most organic solvents and cyclic ester monomers, the polymerizations of monomers such as l-lactide, d-lactide, dl-lactide, ε-caprolactone and other cyclic esters are relatively slow and ineffective. Furthermore, it is difficult to effectively control the molecular weight of the final polymer product which is also contaminated with some residual solid tin(II) alkoxide initiator.